Switchable Site-Selective Benzanilide C(sp2)-H Bromination via Promoter Regulation.

Regioselective benzanilide bromination that generates either regioisomer from the same starting material is desirable. Herein, we develop switchable site-selective C(sp2)-H bromination by promoter regulation. This protocol leads to regiodivergent brominated benzanilide starting from the single substrate via selection of promoters. The protocol demonstrates excellent regioselectivity and good tolerance of functional groups with high yields. The utility effectiveness of this method has been well exemplified in the late-stage modification of biologically important molecules.

Using Lateral Substitution to Control Conformational Preference and Phase Behaviour of Benzanilide-based Liquid Crystal Dimers.

The inclusion of secondary and tertiary benzanilide-based mesogenic groups into liquid crystal dimers is reported as a means to develop new materials. Furthermore, substitution at the nitrogen atom is shown to introduce an additional synthetic 'handle' to modify the molecular structure of the tertiary materials. The design of these materials has proved challenging due to the strong preferences of 3° benzanilides for the E amide conformation. In this work, lateral substitution is used to modify the conformational preferences of the amide linkage and promote liquid crystallinity for a series of N-methyl benzanilide dimers. As the proportion of the E conformer decreases, the nematic-isotropic transition temperatures increase, and enantiotropic nematic behaviour is observed. We also report the synthesis and characterisation of the analogous 2° benzanilide-based materials, which show nematic and twist-bend nematic behaviour. This approach highlights the effects that seemingly small structural modifications, such as the inclusion and position of a methyl group, can have on molecular shape and hence, liquid crystalline behaviour.

Piperidine derivatives as nonprostanoid IP receptor agonists.

The discovery of a new class of nonprostanoid prostaglandin I2 receptor (IP receptor) agonists is reported. Among them, the unique piperidine derivative 31b (2-((1-(2-(N-(4-tolyl)benzamido)ethyl)piperidin-4-yl)oxy)acetic acid) was a good IP receptor agonist and was 50-fold more selective for the human IP receptor than for other human prostanoid receptors. This compound showed good pharmacokinetic properties in dog.

Piperidine derivatives as nonprostanoid IP receptor agonists 2.

We searched for a strong and selective nonprostanoid IP agonist bearing piperidine and benzanilide moieties. Through optimization of substituents on the benzanilide moiety, the crucial part of the agonist, 43 (2-((1-(2-(N-(4-tolyl)benzo[d][1,3]dioxole-5-carboxamido)ethyl)piperidin-4-yl)oxy)acetic acid monohydrate monohydrochloride) was discovered and exhibited strong platelet aggregation inhibition (IC50=21nM) and 100-fold selectivity for IP receptor over other PG receptors. The systemic exposure level and bioavailability after oral administration of 43 were also good in dog.

Reaction of Polyamide Membrane Model Monomers with Chlorine Dioxide: Kinetics, Pathways, and Implications.

Aromatic polyamide (PA) based membranes are widely used for reverse osmosis (RO), but they can be degraded by free chlorine used for controlling the biofouling prior to RO treatment. Kinetics and mechanisms for the reactions of PA membrane model monomers, i.e., benzanilide (BA), and acetanilide (AC), with chlorine dioxide (ClO2) were investigated in this study. Rate constants for the reactions of ClO2 with BA and AC at pH 8.3 and 21°C were determined to be (4.1±0.1) × 10-1 M-1.24 s-1 and (6.0±0.1) × 10-3 M-1 s-1, respectively. These reactions are base assisted with a strong pH dependence. The activation energies of BA and AC degradation by ClO2 were 123.7 and 81.0 kJ mol-1, respectively. This indicates a relatively strong temperature dependence in the studied temperature range of 21-35 °C. The presence of bromide and natural organic matter does not promote the degradation of model monomers by ClO2. BA was degraded by ClO2 via two pathways: (1) the attack on the anilide moiety with the formation of benzamide (major pathway) and (2) oxidative hydrolysis to benzoic acid (minor pathway). A kinetic model was developed to simulate the degradation of BA and formation of byproducts during ClO2 pretreatment, and simulations agree well with the experimental data. Half-lives of BA treated by ClO2 were 1-5 orders of magnitude longer than chlorine under typical seawater treatment conditions. These novel findings suggest the potential application of ClO2 for controlling biofouling ahead of RO treatment at desalination treatments.

Preparation and Characterization of Light-Colored Polyimide Nanocomposite Films Derived from a Fluoro-Containing Semi-Alicyclic Polyimide Matrix and Colloidal Silica with Enhanced High-Temperature Dimensionally Stability.

Light-colored and transparent polyimide (PI) films with good high-temperature dimensional stability are highly desired for advanced optoelectronic applications. However, in practice, the simultaneous achievement of good optical and thermal properties in one PI film is usually difficult due to the inter-conflicting molecular design of the polymers. In the present work, a series of PI-SiO2 nanocomposite films (ABTFCPI) were developed based on the PI matrix derived from hydrogenated pyromellitic anhydride (HPMDA) and an aromatic diamine containing benzanilide and trifluoromethyl substituents in the structure, 2,2'-bis(trifluoromethyl)-4,4'-bis [4-(4-aminobenzamide)]biphenyl (ABTFMB). The inorganic SiO2 fillers were incorporated into the nanocomposite films in the form of colloidal nanoparticles dispersed in the good solvent of N,N-dimethylacetamide (DMAc) for the PI matrix. The derived ABTFCPI nanocomposite films showed good film-forming ability, flexible and tough nature, good optical transparency, and good thermal properties with loading amounts of SiO2 up to 30 wt% in the system. The ABTFCPI-30 film with a SiO2 content of 30 wt% in the film showed an optical transmittance of 79.6% at the wavelength of 400 nm (T400) with a thickness of 25 µm, yellow index (b*) of 2.15, and 5% weight loss temperatures (T5%) of 491 °C, which are all comparable to those the pristine ABTFCPI-0 matrix without filler (T400 = 81.8%; b* = 1.77; T5% = 492 °C). Meanwhile, the ABTFCPI-30 film exhibited obviously enhanced high-temperature dimensional stability with linear coefficients of thermal expansion (CTE) of 25.4 × 10-6/K in the temperature range of 50 to 250 °C, which is much lower than that of the AMTFCPI-0 film (CTE = 32.7 × 10-6/K).

Intrinsically Negative Photosensitive Polyimides with Enhanced High-Temperature Dimensional Stability and Optical Transparency for Advanced Optical Applications via Simultaneous Incorporation of Trifluoromethyl and Benzanilide Units: Preparation and Properties.

Negative photosensitive polyimides (PSPIs) with the photo-patterned ability via the photocrosslinking reactions induced by the i-line (365 nm) and h-line (426 nm) emitting wavelengths in high-pressure mercury lamps have been paid increasing attention in semiconductor fabrication, optical fiber communications, and other advanced optoelectronic areas. In the current work, in view of the optical and thermo-mechanical disadvantages of the currently used negative PSPIs, such as the intrinsically photosensitive or auto-photosensitive systems derived from 3,3',4,4'-benzophenonetetracarboxylic dianhydride (BTDA) and the ortho-alkyl- substituted aromatic diamines, a series of modified negative PSPIs with the enhanced optical transparency in the wavelength of 365~436 nm and apparently reduced coefficients of linear thermal expansion (CTE) were developed. For this purpose, a specific aromatic diamine with both of trifluoromethyl and benzanilide units in the molecular structures, 2,2'-bis(trifluoromethyl)-4,4'-bis[4-(4-amino-3-methyl)benzamide]biphenyl (MABTFMB) was copolymerized with BTDA and the standard 3,3',5,5'-tetramethyl-4,4'-diaminodiphenylmethane (TMMDA) diamine via a two-step chemical imidization procedure. As compared with the pristine PI-1 (BTDA-TMMDA) system, the new-developed fluoro-containing PSPI systems (FPI-2~FPI-7) exhibited the same-level solubility in polar aprotic solvents, including N-methyl-2-pyrrolidone (NMP) and N,N- dimethylacetamide (DMAc). The FPI films cast from the corresponding FPI solutions in NMP showed the optical transmittances of 78.3-81.3% at the wavelength of 436 nm (T436, h-line), which were much higher than that of the PI-1 (T436 = 60.9%). The FPI films showed the CTE values in the range of 40.7 × 10-6/K to 54.0 × 10-6/K in the temperature range of 50 to 250 °C, which were obviously lower than that of PI-1 (CTE = 56.5 × 10-6/K). At last, the photosensitivity of the FPI systems was maintained and the micro-pattern with the line width of 10 µm could be clearly obtained via the standard photolithography process of FPI-7 with the molar ratio of 50% for MABTFMB in the diamine moiety.

More Than Resveratrol: New Insights into Stilbene-Based Compounds.

The concept of a scaffold concerns many aspects at different steps on the drug development path. In medicinal chemistry, the choice of relevant "drug-likeness" scaffold is a starting point for the design of the structure dedicated to specific molecular targets. For many years, the chemical uniqueness of the stilbene structure has inspired scientists from different fields such as chemistry, biology, pharmacy, and medicine. In this review, we present the outstanding potential of the stilbene-based derivatives. Naturally occurring stilbenes, together with powerful synthetic chemistry possibilities, may offer an excellent approach for discovering new structures and identifying their therapeutic targets. With the development of scientific tools, sophisticated equipment, and a better understanding of the disease pathogenesis at the molecular level, the stilbene scaffold has moved innovation in science. This paper mainly focuses on the stilbene-based compounds beyond resveratrol, which are particularly attractive due to their biological activity. Given the "fresh outlook" about different stilbene-based compounds starting from stilbenoids with particular regard to isorhapontigenin and methoxy- and hydroxyl- analogues, the update about the combretastatins, and the very often overlooked and underestimated benzanilide analogues, we present a new story about this remarkable structure.

Study of the inhibitory effects on TNF-α-induced NF-κB activation of IMD0354 analogs.

Nuclear factor-κB (NF-κB) is an important nuclear transcription factor which regulates pro-inflammatory cytokines such as TNF-α, IL-6. Its role as immunoregulatory mediator makes it an attractive target in the development of treatments for inflammatory and autoimmune diseases. In this study, we synthesized derivatives of IMD0354, a known inhibitor for NF-κB, in attempt to understand the effect of benzanilide substitutions on its activity. The inhibition of these analogs on NF-κB activation was analyzed by luciferase assay. The inhibition of IKKß phosphorylation and pro-inflammatory cytokines was determined by Western blot and real-time PCR. The structure activity relationships showed that the hydroxyl group on IMD0354 is a critical moiety that resulting in the inhibition of NF-κB. Derivatives 1m, 2b, and 2c were shown to inhibit pro-inflammatory cytokine production at low concentration. These newly synthesized compounds may be useful for the treatment of chronic inflammatory disorders or for cancer prevention.

Selective anticancer activity of the novel thiobenzanilide 63T against human lung adenocarcinoma cells.

Previously, it has been reported that molecules built on the benzanilide and thiobenzanilide scaffold are the promising groups of compounds with several biological activities including antifungal, antimycotic, antibacterial, spasmolytic, and anticancer ones. In this study the mechanism of action of one selected thiobenzanilide derivative N,N'-(1,2-phenylene)bis3,4,5-trifluorobenzothioamide (63T) with strongest cytotoxic activity has been investigated for the first time in human lung adenocarcinoma (A549) and normal lung derived fibroblast (CCD39Lu) in a cell culture model. The results demonstrated, that 63T can be considered a selective anticancer compound. Based on these results, several experiments including the analysis of cellular morphology, cell phase distribution, cytoplasmic histone-associated DNA fragmentation, apoptosis, necrosis, and autophagy detection were performed to understand better the mechanism underlying the anticancer activity. The data showed that 63T is a small molecule compound, which selectively induces cancer cell death in a caspase independent pathway; moreover, the autophagic dose-dependent processes may be involved in the mechanism of cell death.

Crystal structure of N-(2-hy-droxy-5-methyl-phen-yl)benzamide.

In the title compound, C14H13NO2, the mean plane of the non-H atoms of the central amide fragment C-N-C(=O)-C (r.m.s. deviation = 0.029 Å) forms dihedral angles of 5.63 (6) and 10.20 (5)° with the phenyl and hy-droxy-phenyl rings, respectively. A short intra-molecular N-H⋯O contact is present. In the crystal, the mol-ecules are linked by O-H⋯O hydrogen bonds to generate C(7) chains along [100]. The chains are reinforced by weak C-H⋯O contacts, which together with the O-H⋯O bonds lead to R 2 (2)(7) loops. Very weak N-H⋯O inter-actions link the mol-ecules into inversion dimers.